Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.Accepted

Rhinitis, perennial and seasonal allergic or vasomotor (prophylaxis and treatment) or
Conjunctivitis, allergic (prophylaxis and treatment)—Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis , vasomotor rhinitis , and allergic conjunctivitis due to inhalant allergens and foods.{02}{12}{13}{48}

Pruritus (treatment)
Urticaria (treatment)
Angioedema (treatment)
Dermatographism (treatment) or
Transfusion reactions, urticarial (treatment)— Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. Cyproheptadine may be particularly useful for cold urticaria,{02}{12}{14}dermatitis including neurodermatitis and neurodermatitis circumscripta, eczema, eczematoid dermatitis, mild local allergic reactions to insect bites, angioneurotic edema, drug and serum reactions, anogenital pruritus and pruritus of chickenpox. {48} [Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea.]1

Sneezing (treatment) or
Rhinorrhea (treatment)—Antihistamines are indicated for the relief of sneezing and rhinorrhea associated with the common cold {12}. However, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. Non-sedating (i.e., second-generation) antihistamines are unlikely to be useful in the treatment of the common cold symptoms since they do not have clinically significant anticholinergic effects (e.g., drying effects on nasal mucosa). {15}

Anaphylactic or anaphylactoid reactions (treatment adjunct)—Antihistamines are indicated as adjunctive therapy to epinephrine and other standard measures for anaphylactic reactions after the acute manifestations have been controlled, and to ameliorate the allergic reactions to blood or plasma.{02}{12}{48}

Anxiety (treatment) and
Tension, psychosis-related (treatment)—Hydroxyzine is indicated for the relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. The effectiveness of hydroxyzine as an antianxiety agent for long-term use (for example, more than 4 months) has not been assessed by systematic clinical studies. {12}

Parkinsonism (treatment)1 or
Extrapyramidal reactions, drug-induced (treatment) 1—Diphenhydramine is indicated for the symptomatic treatment of parkinsonism and drug-induced extrapyramidal reactions in elderly patients unable to tolerate more potent antidyskinetic medications, for mild cases of parkinsonism in other age groups and, in combination with centrally acting anticholinergic agents, for other cases of parkinsonism. {12}

Cough (treatment)—Diphenhydramine hydrochloride syrup is currently indicated as a non-narcotic cough suppressant for control of cough due to colds or allergy. {12}

Motion sickness (prophylaxis and treatment) or
Vertigo (treatment)—Dimenhydrinate and diphenhydramine are indicated for the prevention and treatment of the nausea, vomiting, dizziness, or vertigo of motion sickness. {12}

Nausea or vomiting (prophylaxis and treatment)— Parenteral hydroxyzine is indicated for the control of nausea and vomiting, excluding nausea and vomiting of pregnancy. {12}

Sedation—Diphenhydramine and hydroxyzine are indicated for their sedative and hypnotic effects and as preoperative medications. {12}

Insomnia (treatment)—Diphenhydramine and doxylamine are indicated as nighttime sleep aids to help reduce the time to fall asleep in patients having difficulty falling asleep. {12}

Analgesia adjunct, during surgery
Anesthesia, general, adjunct or
Anesthesia, local, adjunct—Parenteral hydroxyzine is useful as pre- and postoperative, and pre- and postpartum adjunctive medication to allow reduction in narcotic dosage, and to control anxiety and emesis. {12}

[Appetite, lack of (treatment)]—Cyproheptadine is used as an appetite stimulant, in adults and children.

[Headache, vascular (treatment)]—Cyproheptadine is used for treatment of vascular headaches, such as migraine and histamine cephalalgia.{48}
[Asthma, bronchial (treatment adjunct) ]1—Cetirizine, and loratadine are used as adjunctive treatment to asthma medications to reduce symptoms and improve bronchodilation in patients with mild atopic asthma. {17}{18}{19}{20}Unaccepted
Cyproheptadine has been used in the treatment of Cushing's disease because of its pronounced antiserotonin properties, which may decrease corticotropin release. Cyproheptadine may also provide antidiarrheal action against intestinal hypermotility associated with the excessive production of serotonin in patients with carcinoid tumors, and in some other conditions involving the release of serotonin. However, there is no conclusive evidence of effectiveness for these uses.

Antihistaminic (H 1-receptor)—Antihistamines used in the treatment of allergy act by competing with histamine for H 1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa.

Antianxiety agent—Hydroxyzine's sedative action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system (CNS). It is not a cortical depressant.

Antidyskinetic—The actions of diphenhydramine in parkinsonism and in drug-induced dyskinesias appear to be related to a central inhibition of the actions of acetylcholine, which are mediated via muscarinic receptors (anticholinergic action), and to its sedative effects.

Antiemetic; antivertigo agent—The mechanism by which some antihistamines exert their antiemetic, anti–motion sickness, and antivertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect.

Antitussive—Diphenhydramine suppresses the cough reflex by a direct effect on the cough center in the medulla of the brain.

Sedative-hypnotic—Most antihistamines cross the blood-brain barrier and produce sedation due to inhibition of histamine N-methyltransferase and blockage of central histaminergic receptors. Antagonism of other central nervous system receptor sites, such as those for serotonin, acetylcholine, and alpha-adrenergic stimulation, may also be involved. Central depression is not significant with cetirizine (low doses), desloratadine, or loratadine because they do not readily cross the blood-brain barrier. Also, they bind preferentially to peripheral H 1-receptors rather than to central nervous system H 1-receptors.{03}

Appetite stimulant—Cyproheptadine competes with serotonin for receptor sites, thus blocking the responses to serotonin in vascular, intestinal, and other smooth muscles. It is possible that by altering serotonin activity in the appetite center of the hypothalamus, cyproheptadine stimulates appetite.

Antiasthmatic— Cetirizine, and loratadine have been shown to cause mild bronchodilation and also to block histamine-induced bronchoconstriction in asthmatic patients. Also, loratadine, have been shown to diminish exercise-induced bronchospasm and hyperventilation-induced bronchospasm. Cetirizine has not been shown to be uniformly effective in preventing allergen- or exercise-induced bronchoconstriction; however, due to its inhibition of late-phase eosinophil recruitment after local allergen challenge, it has been shown to be more effective, in higher doses, than other antihistamines in reducing the symptoms of pollen-induced asthma.

Other actions/effects:

Anticholinergic—Antihistamines prevent responses to acetylcholine that are mediated via muscarinic receptors. The ethanolamine derivatives may show greater anticholinergic activity than the other classes of antihistamines. Loratadine, has no significant anticholinergic activity; cetirizine has minimal anticholinergic activity.

Anesthetic, local, dental—Antihistamines are structurally related to local anesthetics and have local anesthetic activity. Local anesthetics prevent the initiation and transmission of nerve impulses by decreasing the permeability of the nerve cell membrane to sodium ions. This action decreases the rate of depolarization of the membrane and prevents the generation of the action potential.Absorption:

Well absorbed after oral administration.

Note: Ingestion of food may enhance the absorption of loratadine by 40% and of its active metabolite by 15%{03}.
Food may delay the rate, but not the extent of cetirizine absorption.
In one study involving patients 66 to 78 years of age the extent of absorption and peak plasma levels of loratadine and its metabolite were significantly higher (55%) than those in studies with younger patients.{03}
Desloratadine's absorption is not affected by food. Renal impairment and hepatic impairment requires dosage adjustments due to increased AUC (area under the concentration time curve).{51}

Hepatic (cytochrome P-450 system); some renal. Of the second-generation antihistamine , loratadine is metabolized by the hepatic cytochrome P-450 system and have active metabolites{03}; however, cetirizine is minimally metabolized and excreted unchanged primarily through the kidneys.

Desloratadine is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzymes responsible for the metabolism have not been identified{51}{52}.Half-life:

Elimination:
Most of the antihistamines studied (except cetirizine) are excreted as metabolites within 24 hours.

Cetirizine—
Approximately 60% of the total dose administered is excreted unchanged in urine within 24 hours; about 10% is excreted in feces.

Desloratadine—
Approximately 87% of a 14C-desloratadine dose was equally recovered in urine and feces. {51}{52}

Loratadine—
Approximately 80% of the total dose administered is excreted equally in urine and feces in the form of metabolic products within 10 days.{03} Twenty-seven percent of the total dose is excreted in the urine in the conjugated form within 24 hours.

Clearance

Cetirizine

The weight-normalized, apparent total body clearance was 33% greater in children aged 7 to 12 years than in adults and 81% to 111% greater in children aged 2 to 5 years than in adults{46}.

Patients with moderate renal impairment had a 70% decrease in clearance compared to normal volunteers{46}.

Precautions to ConsiderCross-sensitivity and/or related problems

Patients sensitive to one of the antihistamines may be sensitive to others.Carcinogenicity/Tumorigenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic, tumorigenic, or mutagenic potential of most antihistamines have not been performed.

Cetirizine

In a 2–year study, cetirizine was not carcinogenic in rats given dietary doses up to 15 times the maximum recommended human daily oral dose for adults and 10 times the maximum recommended human daily oral dose for children on a mg/m2 basis{46}. In another 2–year study in male mice, cetirizine increased the incidence of benign liver tumors at a dose of 6 times the adult maximum recommended daily dose and 4 times the maximum pediatric dose on a mg/m 2 basis{46}. The clinical significance of these findings during long-term use of cetirizine is not known.

Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and the in vivo micronucleus test in rats{46}.

Desloratadine

The carcinogenic potential of desloratadine was assessed using loratadine studies.{51}

Fexofenadine

The carcinogenic and reproductive toxicity of fexofenadine were assessed using terfenadine# studies with adequate fexofenadine exposure. No evidence of carcinogenicity was observed in an 18 month study in mice and in a 24 month study in rats at oral doses of up to 150 mg/kg of terfenadine# (which led to fexofenadine exposures that were respectively approximately 3 to 5 times the exposure from the maximum recommended daily oral dose of fexofenadine in adults and children).{49}

In carcinogenicity studies, AUC data demonstrated that the exposure of mice given loratadine 40 mg/kg was 3.6 (loratadine) and 18 (active metabolite) times higher than that for a human given 10 mg/day. Exposure of rats given 25 mg/kg was 28 (loratadine) and 67 (active metabolite) times higher than that for a human given 10 mg/day. Male mice given 40 mg/kg had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg and males and females given 25 mg/kg. The clinical significance of these findings during long-term use of loratadine is not known. {03}

Studies in mice and rats have not shown evidence of tumorigenicity when terfenadine# was given in oral doses approximately 5 and 10 times the maximum recommended human daily dose on a mg per square meter of body surface area basis, respectively. Microbial and micronucleus test assays with terfenadine# have not shown evidence of mutagenesis. {08}

Pregnancy/Reproduction

Pregnancy—
Animal studies have suggested that meclizine and cyclizine, chemically related to antihistamines, might have a teratogenic potential

Desloratadine was not teratogenic in rats at doses up to 48 mg/kg/day, or in rabbits at doses up to 60 mg/kg/day.{51}

In a separate study, an increase in pre-implantation loss and a decreased number of implantations and fetuses were noted in female rats at 24 mg/kg. Reduced body weight and slow righting reflex were reported in pups at doses of 9 mg/kg/day or greater. Desloratadine had no effect on pup development at an oral dose of 3 mg/kg/day.{51}

Studies in rats and rabbits at doses up to 5 times the human dose have revealed no evidence of impaired fertility or harm to the fetus.

FDA Pregnancy Category B.

Doxylamine

The Food and Drug Administration has stated that human epidemiologic data have not produced convincing evidence that the doxylamine and pyridoxine combination, a medication previously prescribed to treat nausea and vomiting during pregnancy, causes diaphragmatic hernias or other birth defects.

Adequate and well-controlled studies in humans have not been done.{49}

Studies done in rats and rabbits showed no evidence of teratogenicity. Oral doses of terfenadine# up to 300 mg/kg (which led to fexofenadine exposures that were approximately 3 times the maximum recommended daily oral dose of fexofenadine in adults.{49}

Nonteratogenic effects were seen as dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of 150 mg/kg of terfenadine# (approximately 3 times the maximum daily oral dose of fexofenadine in adults based on comparison of fexofenadine AUCs). {49}

Adequate and well-controlled studies in humans have not been done. However, hydroxyzine is not recommended for use in the early months of pregnancy since studies in rats have shown that it causes fetal abnormalities when given in doses substantially above the human therapeutic range.

First-generation antihistamines may inhibit lactation because of their anticholinergic actions.

Small amounts of antihistamines are distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants.

The extent of distribution into human breast milk is unknown. Studies in dogs indicated that approximately 3% of the dose is distributed into milk {01}.

Loratadine:

Loratadine and its metabolite descarboethoxyloratadine are distributed into breast milk, achieving concentrations equivalent to plasma levels. In one study, approximately 0.03% of the administered dose was distributed into breast milk over 48 hours after maternal ingestion of a single oral dose of 40 mg.

Pediatrics

Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system (CNS) excitation, and an increased tendency toward convulsions.

A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines.

Cetirizine, and loratadine:

Although adequate and well-controlled studies have not been done in the pediatric population, loratadine, is not likely, and cetirizine is less likely than first-generation antihistamines, to cause anticholinergic or significant CNS effects in children.

Desloratadine:

No information is available on the relationship of age to the effects of desloratadine in children under 12 years of age. Safety and efficacy have not been established.

Fexofenadine:

In two placebo controlled trials, the safety of fexofenadine in 6 to 11 year old pediatric patients was established for treatment of seasonal allergic rhinitis and was found to significantly reduce total symptom scores.{49}

Based on a extrapolation of the demonstrated efficacy in adults, the safety of fexofenadine in 6 to 11 year old pediatric patients for the treatment of chronic idiopathic urticaria is established.{49}

Adolescents

Desloratadine

Desloratadine is approved for use in adolescents 12 years of age and older.{51}

Geriatrics

Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines.

A paradoxical reaction characterized by hyperexcitability may occur in geriatric patients taking antihistamines.

Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued.

Desloratadine, cetirizine, and loratadine:

Desloratadine, and Loratadine are not likely, and cetirizine is less likely than first-generation antihistamines, to cause anticholinergic or significant CNS effects in geriatric patients {14}{51}. However, because elderly patients are more likely to have age-related renal function impairment, cetirizine and loratadine may accumulate and cause anticholinergic or CNS effects when given in such patients at the usual adult dose {01}{03}.

Pharmacogenetics

Desloratadine has higher peak plasma concentration and area under the curve values in females compared with males and in African-Americans compared with Caucasian patients. However, no dosage adjustments are recommended in either case.{51}

Dental

Prolonged use of antihistamines (except cetirizine, desloratadine, or loratadine) may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.# Products containing terfenadine were withdrawn from the U.S. market by the Food and Drug Administration in February 1998 and from the Canadian market by the Health Protection Branch, Health Canada in August 1998Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: It is not likely that cetirizine, desloratadine, or loratadine will interact with most of the following medications because they lack significant anticholinergic and CNS actions. However, cetirizine and loratadine have been shown to cause dose-related CNS effects (e.g., sedation); and cetirizine has minimal anticholinergic effects.{01}{03}{14}{51}
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antacids, magnesium or aluminum containing (administration of fexofenadine within 15 minutes of an aluminum or magnesium containing antacid decreased fexofenadine AUC by 41% and C max by 43%.{49})

» Alcohol or» CNS depression–producing medications, other (see Appendix II ) (concurrent use may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications)

» Anticholinergics or other medications with anticholinergic activity (see Appendix II ) (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy)

Apomorphine (prior administration of dimenhydrinate, diphenhydramine, doxylamine, or hydroxyzine may decrease the emetic response to apomorphine in the treatment of poisoning)

Potent inhibitors of the cytochrome P450 enzyme system such as:
Erythromycin
Fluconazole
Itraconazole
Ketoconazole
Metronidazole
Miconazole (concurrent use of these medications may increase plasma levels of loratadine; there are no reports to date of serious ventricular arrhythmias associated with increased plasma levels of loratadine)

(concurrent use of fexofenadine with co-administered ketoconazole and erythromycin may lead to increased plasma levels of fexofenadine, and may also enhance fexofenadine gastrointestinal absorption and decrease fexofenadine gastrointestinal excretion{49})

» Monoamine oxidase (MAO) inhibitors, including furazolidone and procarbazine (concurrent use of MAO inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended)

{48}
Ototoxic medications (see Appendix II ) (concurrent use with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo)

Photosensitizing medications, other (concurrent use of these medications with antihistamines may cause additive photosensitizing effects)

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

For hydroxyzine (in addition to those listed for all antihistamines) :
Urine 17-hydroxycorticosteroid determinations (false increases have been reported with concurrent use of hydroxyzine)

With physiology/laboratory test values

For cyproheptadine
Amylase and
Prolactin (serum concentrations may be increased when cyproheptadine is administered with thyrotropin-releasing hormone)

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problems exist:» Hepatic function impairment (desloratadine dosage adjustment recommended due to increases in bioavailability, half-life, and area under the curve.{51})

» Renal function impairment (Desloratadine dosage adjustment is recommended due to increases in plasma concentration and area under the curve{51})

Glaucoma, open-angle (anticholinergic mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted)

Hypersensitivity to the antihistamine used
Caution is recommended when dimenhydrinate, diphenhydramine, or hydroxyzine is used, since their antiemetic action may impede diagnosis of such conditions as appendicitis and obscure signs of toxicity from overdosage of other drugs.For cyproheptadine:» Peptic ulcer, stenosing{02}» Pyloroduodenal obstruction{02}{48} (anticholinergic effects of cyproheptadine may exacerbate these conditions )

For desloratadine:
Metabolism of desloratadine, impaired (slow metabolizers of desloratadine may be more susceptible to dose-related adverse events {51})

Those indicating need for medical attention only if they continue or are bothersomeIncidence more frequentDrowsinessdryness of mouth, nose, or throatgastrointestinal upset, stomach pain, or nausea —with azatadine, diphenhydramine, , and tripelennamine

headache —with desloratadine{51}increased appetite or weight gain —with , cyproheptadinepharyngitis (body aches or pain ; congestion ; cough; dryness or soreness of throat; fever; hoarseness; runny nose; tender, swollen glands in neck; trouble in swallowing ; voice changes)— with desloratadine. {51}thickening of mucus —with azatadine and cyproheptadine{02}{03}{04}{08}{10}{12}{26}{28}{30}{33}{34}{35}{36}{37}{38}{39}{40}{41}{42}{43}{44}{45}Note: Tolerance to central nervous system effects may develop quickly with some antihistamines, so that sedation is no longer troublesome after a few days.
Incidence of sedation may increase when the recommended doses of loratadine are exceeded.

Note:Confusion; difficult or painful urination; drowsiness; dizziness; and dryness of mouth, nose, or throat are more likely to occur in the elderly.Nightmares, unusual excitement, nervousness, restlessness, or irritability is more likely to occur in children and elderly patients.

Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).Clinical effects of overdoseSymptoms of overdoseAnticholinergic effects (clumsiness or unsteadiness; severe drowsiness; severe dryness of mouth, nose, or throat ; flushing or redness of face; shortness of breath or troubled breathing)— especially with azatadine and clemastine{35}{39}cardiac arrhythmias (fast or irregular heartbeat)—{04}{34}{42} ; less frequent with azatadine and clemastineCNS depression (severe drowsiness)CNS stimulation (hallucinations, seizures, trouble in sleeping)hypotension (feeling faint)Note:Anticholinergic and CNS stimulant effects are more likely to occur in children with overdose. Hypotension may also occur in the elderly at usual doses.
Anticholinergic and CNS effects may be less likely to occur with , cetirizine, desloratadine or, loratadine, than with the first-generation antihistamines.

Specific treatment:
Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure.

Oxygen and intravenous fluids.

Precaution against use of stimulants (analeptic agents) because they may cause seizures.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antihistamines (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):Before using this medication» Conditions affecting use, especially:Sensitivity to any antihistamine

Pregnancy—Not taking during early months of pregnancy because of fetal abnormalities in studies in animals (for hydroxyzine only)

Breast-feeding—Use not recommended; may cause unusual excitement or irritability in nursing infant

Use in children——Increased susceptibility to anticholinergic side effects in newborn or premature infants; hyperexcitability (paradoxical reaction) may occur in children

Use in the elderly—— Increased susceptibility to anticholinergic side effects; hyperexcitability (paradoxical reaction) may occur

For dimenhydrinate and diphenhydramine when used as antivertigo agent
Taking at least 30 minutes (preferably 1 to 2 hours) before travelingPrecautions while using this medication
Possible interference with skin tests using allergens; need to inform physician if using medication

May mask ototoxic effects of large doses of salicylates

» Avoiding use of alcohol or other CNS depressants

» Caution if drowsiness occurs

Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

For dimenhydrinate, diphenhydramine, or hydroxyzine
Need to inform physician of use: Possible interference with diagnosis of appendicitis; may mask signs of toxicity from overdosage of other drugs

For diphenhydramine and doxylamine when used in the treatment of insomnia» Not using concurrently with other sedatives or tranquilizers

For oral dosage forms only
Most antihistamines may be taken with food, water, or milk to lessen gastric irritation.

For parenteral dosage forms only
Intramuscular injections should be administered deeply into the muscle.

Intravenous injections should be administered slowly, preferably with the patient in a recumbent position.

For hydroxyzine:
Administration should be by deep intramuscular injection into a large muscle mass, preferably the upper outer quadrant of the buttock or the mid-lateral thigh.

Intramuscular injections should not be made into the lower or mid-third of the upper arm.

When used preoperatively or prepartum, narcotic requirements may be decreased as much as 50%.

Note: Products containing terfenadine were withdrawn from the U.S. market by the Food and Drug Administration in February 1998 and from the Canadian market by the Health Protection Branch, Health Canada in August 1998.

Note: Products containing astemizole were withdrawn from the U.S. and Canadian markets by the manufacturer in June 1999.

Usual adult prescribing limits
Up to 40 mg daily.Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Intramuscular, intravenous, or subcutaneous, 125 mcg (0.125 mg) per kg of body weight or 3.75 mg per square meter of body surface three or four times a day as needed.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.

Strength(s) usually available
U.S.—

10 mg per mL (Rx) [Nasahist B][Generic]

Canada—
Not commercially available.Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.Stability:
Crystallization may occur if cooled below 0 °C (32 °F); but on warming to 30 °C (86 °F), the crystals will redissolve.Additional information:
The period of protection provided by a single dose ranges from three to twelve hours.

Note: In patients with reduced creatinine clearance (< 31 mL per min) and with hepatic impairment, a dose of 5 mg once a day is recommended {01}.

Usual adult prescribing limits
10 mg a day {01}.Usual pediatric dose
Antihistaminic (H 1-receptor)1
Children up to 2 years of age: Safety and efficacy have not been established. {26}{46}

Children 2 to 6 years of age: Oral, 2.5 mg once a day. The dosage may be increased to a maximum daily dose of 5 mg, given as 5 mg once a day or 2.5 mg every 12 hours. {26}{46}

Children 6 years of age and older: Oral, 5 or 10 mg once a day. {01}{26}{46}

Note: The dosage should be decreased in patients who have reduced renal function (creatinine clearance of 11–31 mL per minute) or hepatic function impairment. In patients up to 6 years of age with renal or hepatic dysfunction, cetirizine use is not recommended. For children 6 years of age and older, the lower dosage of 5 mg once a day should be used. {26}{46}

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.CYPROHEPTADINE HYDROCHLORIDE SYRUP USPUsual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, initially 4 mg every eight hours, the dosage being increased as needed. For most patients the therapeutic range is 4 to 20 mg a day. However, doses up to 32 mg a day have been used occasionally. {48}

[Vascular headache suppressant ]
Initial: Oral, 4 mg at the start of the attack, repeated after thirty minutes if necessary.{48}

CYPROHEPTADINE HYDROCHLORIDE TABLETS USPUsual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, initially 4 mg every eight hours, the dosage being increased as needed. For most patients the therapeutic range is 4 to 20 mg a day. However, doses up to 32 mg a day have been used occasionally. {02}

[Appetite stimulant]
Oral, 4 mg three times a day with meals.

Note: Treatment period to promote weight gain should not exceed six months.

[Vascular headache suppressant ]
Initial: Oral, 4 mg at the start of the attack, repeated after thirty minutes if necessary.

• Children 2 to 6 years of age: Oral, 2 mg every eight to twelve hours as needed, not to exceed 12 mg per day {02}.

• Children 7 to 14 years of age: Oral, 4 mg every eight to twelve hours as needed, not to exceed 16 mg per day {02}.

[Appetite stimulant]
Children 2 to 6 years of age: Oral, initially 2 mg two or three times a day with meals. The dosage may be increased, if necessary, but not to exceed 8 mg a day.

Children 7 to 14 years of age: Oral, initially 2 mg three or four times a day with meals. The usual maintenance dose is 4 mg two or three times a day. The dosage may be increased, if necessary, but not to exceed 16 mg a day.

Note: Premature and full-term neonates—Use is not recommended.
Treatment period to promote weight gain should not exceed 3 months.

Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 12 years of age: Oral, 150 mcg (0.15 mg) per kg of body weight or 4.5 mg per square meter of body surface per day, in four divided doses or for

• Children 2 to 5 years of age: Oral, 500 mcg (0.5 mg) every four to six hours as needed.

• Children 5 to 12 years of age: Oral, 1 mg every four to six hours as needed.

When dimenhydrinate is used for prophylaxis of motion sickness, it should be taken at least 30 minutes, and preferably 1 or 2 hours, before exposure to conditions that may precipitate motion sickness.For parenteral dosage form only

DIMENHYDRINATE ORAL SOLUTIONUsual adult and adolescent dose
Antiemetic or
Antivertigo agent
Oral, 50 to 100 mg every four to six hours. {10}{27}

Usual adult prescribing limits
400 mg per 24 hours. {10}{27}Usual pediatric dose
Antiemetic or
Antivertigo agent
Children 2 to 6 years of age: Oral, 12.5 to 25 mg every six to eight hours as needed, not to exceed 75 mg per day {10}{27}.

Children 6 to 12 years of age: Oral, 25 to 50 mg every six to eight hours as needed, not to exceed 150 mg per day {10}{27}.

Intravenous, 50 mg in 10 mL of 0.9% sodium chloride injection, administered slowly over a period of at least two minutes, repeated every four hours as needed.

Usual pediatric dose
Antiemetic or
Antivertigo agent
Intramuscular, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, every six hours as needed, not to exceed 300 mg per day.

Intravenous, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, in 10 mL of 0.9% sodium chloride injection, administered slowly over a period of at least two minutes, every six hours as needed, not to exceed 300 mg per day.

Note: The 50-mg-per-mL concentration is intended for intramuscular use. To use this concentration for intravenous administration, the solution must be further diluted at a ratio of at least 1:10 (10 mL of diluent for each 1 mL of dimenhydrinate) with a compatible intravenous solution, such as sterile saline or 5% dextrose in water. {27}

When diphenhydramine is used for prophylaxis of motion sickness, it should be taken at least 30 minutes, and preferably 1 or 2 hours, before exposure to conditions that may precipitate motion sickness.

Antiemetic or
Antivertigo agent
Intramuscular or intravenous, 10 mg initially, may be increased to 20 to 50 mg every two to three hours.

Usual adult prescribing limits
Up to 100 mg per dose or 400 mg daily.Usual pediatric dose
Antihistaminic (H 1-receptor) or
Antidyskinetic
Intramuscular, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface, four times a day, not to exceed 300 mg per day.

Antiemetic or
Antivertigo agent
Intramuscular, 1 to 1.5 mg per kg of body weight every six hours, not to exceed 300 mg per day.

Oral Dosage FormsTRIPELENNAMINE CITRATE ELIXIR USPUsual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, the equivalent of tripelennamine hydrochloride: 25 to 50 mg every four to six hours as needed.

Usual adult prescribing limits
Up to the equivalent of 600 mg of tripelennamine hydrochloride daily.Usual pediatric dose
Antihistaminic (H 1-receptor)
Oral, the equivalent of tripelennamine hydrochloride, 1.25 mg per kg of body weight or 37.5 mg per square meter of body surface every six hours as needed, not to exceed 300 mg per day.